title: Expression of the antimicrobial peptide cathelicidin in myeloid cells is required for lung tumor growth.
abstract: Antimicrobial peptides, such as the cathelicidin LL-37/hCAP-18 and its mouse homolog cathelicidin-related antimicrobial peptide (CRAMP), are important effectors of the innate immune system with direct anti-bacterial activity. Cathelicidin is possibly involved in the regulation of tumor cell growth. The aim of this study was to characterize the role of cathelicidin expressed in non-tumorous cells in a preclinical mouse model of tumor growth. Wild-type and CRAMP-deficient animals were exposed to cigarette smoke (CS) and Lewis lung carcinoma cells were injected to initiate the growth of tumors in the lung. CS exposure significantly increased the proliferation of lung tumors in wild-type mice, but not in CRAMP-deficient mice. CS exposure induced the recruitment of myeloid cell into tumor tissue in a CRAMP-dependent manner. Mice lacking RelA/p65 specifically in myeloid cells showed impaired recruitment of CRAMP-positive cells into the lung. In vitro studies with human cells showed that LL-37/hCAP-18 in macrophages is induced by soluble factors derived from cancer cells. Taken together, these data indicate that cathelicidin expressed from myeloid cells promotes CS-induced lung tumor growth by further recruitment of inflammatory cells. The regulation of cathelicidin expression involves myeloid p65/RelA and soluble factor from tumor cells.
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Homburg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Homburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Beisswenger
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Homburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Herr
authors.affiliation: Department of Internal Medicine II, Technical University of Munich, Munich, Germany.
authors.forename: R M
authors.initials: RM
authors.lastname: Schmid
authors.affiliation: Division of Dermatology, University of California, San Diego, CA, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Gallo
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Homburg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Han
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Homburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Zakharkina
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Homburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Bals
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000378:metabolism* / Q000556:secondary; D054804:Cathelicidins / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism*; D009368:Neoplasm Transplantation; D012907:Smoking / Q000009:adverse effects; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D047368:Tumor Burden
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; C498144:Rela protein, mouse; D051996:Transcription Factor RelA